Molecular dynamics simulations of the enzyme Catechol-O-Methyltransferase: methodological issues1 |
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| Authors: | A Bunker PT Männistö J-F St Pierre T Róg P Pomorski L Stimson |
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| Institution: | 1. Drug Discovery and Development Technology Center , Faculty of Pharmacy, University of Helsinki , Finland alex.bunker@helsinki.fi;3. Division of Pharmacology and Toxicology , Faculty of Pharmacy, University of Helsinki Finland , Québec, Canada;4. Division of Pharmacology and Toxicology , Faculty of Pharmacy, University of Helsinki Finland , Québec, Canada;5. Département de Physique and Regroupement Québécois sur les Matériaux de Pointe , Université de Montréal Montreal , Québec, Canada;6. Laboratory of Physics, Helsinki University of Technology Finland , Kraków, Poland;7. Department of Biophysics , Faculty of Biotechnology, Jagiellonian University , Kraków, Poland;8. Department of Applied Mathematics , The University of Western Ontario , London, Ontario, Canada |
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| Abstract: | Results from extensive 70 ns all-atom molecular dynamics simulations of catechol-O-methyltransferase (COMT) enzyme are reported. The simulations were performed with explicit TIP3P water and Mg2?+ ions. Four different crystal structures of COMT, with and without different ligands, were used. These simulations are among the most extensive of their kind and as such served as a stability test for such simulations. On the methodological side we found that the initial energy minimization procedure may be a crucial step: particular hydrogen bonds may break, and this can initiate an irreversible loss of protein structure that becomes observable in longer time scales of the order of tens of nanoseconds. This has important implications for both molecular dynamics and quantum mechanics–molecular mechanics simulations. |
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| Keywords: | catechol-O-methyltransferase COMT molecular dynamics hydrogen bonds stability protein dynamics |
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